Researchers at the Sanford Burnham Prebys Medical Discovery Institute (SBP) and colleagues have identified a protein that regulates T cell responses, which might explain why the immune system sometimes fails to eradicate chronic infections or properly fight growing tumors. Additionally, the manipulation of the protein’s expression may point to a new therapeutic approach for many diseases, including autoimmune conditions such as rheumatoid arthritis.
The findings, revealed in the research paper “PSGL-1 Is an Immune Checkpoint Regulator that Promotes T Cell Exhaustion,” were published in Immunity.
T cells are immune cells that recognize and eliminate foreign pathogens, such as bacteria and viruses, and fight against abnormal growing cells such as tumor cells. T cell activities are dependent on signals from other cells, which modulate and tune T cells’ responses according to the posing threat. Sometimes the responses are not adequate, which leads to autoimmunity (healthy cells turning against each other.)
Researchers found that a protein on the surface of T cells, P-selectin glycoprotein ligand-1 (PSGL-1), acts as a negative regulator of T cell function, leading to the exhaustion of T cells in viral and tumor mouse models. The scientists observed that PSGL-1 is required to increase levels of immune checkpoints to allow T cell inhibition and that, when the protein is absent, T cells are active for much longer than normal.
“Blocking PSGL-1 may enhance the immune response to cancer and chronic viral infections such as hepatitis. In contrast, activating PSGL-1 may be a way to inhibit immune responses that could potentially be used to treat autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis and lupus,” lead author Linda Bradley said in a news release.
Using a mouse model engineered to lack PSGL-1, the team found that lymphocytic choriomeningitis virus (LCMV) infections that normally last several months were quickly eradicated. Also, melanoma tumors in these animals grew much slower. The approach has gathered increasing interest by pharmaceutical companies, as it represents a possible anti-cancer treatment and therapy in diseases where T cell responses are known to be dysregulated, such as autoimmune diseases.